Dual growth factor delivery to achieve therapeutic neovascularization

双生长因子递送以实现治疗性新血管形成

• 批准号: 0853996
• 负责人: Laura Suggs
• 金额: $ 30万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0853996&HistoricalAwards=false
• 关键词: Dual; growth; factor; delivery; achieve

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0853996SuggsThe goal of the PI is to make a significant contribution in cardiovascular tissue engineering though research, education, and the transformation of stem cell engineering. In this context, stem cell engineering includes the design of cell and drug delivery constructs for regenerative medicine and the elucidation of fundamental scientific principles underlying cell-mediated repair. The objective of this proposal is to create a cell-free, dual growth factor delivery system to recruit endogenous progenitors and promote their long-term survival as well as to test the efficacy of this combination strategy in promoting neovascularization and improving cardiac function. The success of this proposal would enable the PI to establish a program in the area of cardiac engineering with a particular focus on designing cell and drug delivery systems. Cardiac stem cell therapy has demonstrated limited efficacy in clinical trials, but will only become a reality through robust cell engineering processes. This approach has the potential to transform stem cell therapy through harnessing the body's own stem cells. Furthermore, the PI's engineering approach will be used as a platform around which a series of educational and outreach goals will be met.Intellectual Merit: Progress in engineering novel techniques for scaffold synthesis and processing may allow for entry into the new phase of cardiac therapy. Natural and synthetic matrices have shown promise as tools to deliver growth factors and cells; however, to date none of these constructs have exhibited the necessary temporal and spatial control. The combination of delivering multiple growth factors to provide mobilization and survival of resident stem cells in a precisely organized presentation provides a realistic solution to the challenge of cardiac therapy. The PI will investigate whether the system can deliver multiple growth factors with controlled release kinetics. The efficacy of a combination strategy (synergistic stem cell recruitment and sustained cell viability) will be evaluated, and the underlying mechanisms will be explored. Broader Impact: The promise of cardiac regeneration can only be realized through solutions engineered on a molecular and cellular level. It is a goal of the current project to serve two functions: (1) to design a unique delivery platform from which stem cell organization can be controlled and (2) to elucidate fundamental mechanisms underlying cell-mediated cardiac repair. The educational and outreach goals are tightly linked via the ideological concept of engineering design. As a junior faculty, the PI has conceived of and implemented the entire BME senior design sequence at UT Austin. She has a strong and continuing passion for design and its instruction and proposes that design should be integrated at all educational levels. The outreach activities described in this proposal extend from pre-college through the level of the undergraduate student. Specific tools will be developed including teaching modules, online course resources, as well as instructional tools for use by existing pre-college outreach programs.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）0853996建议PI的目标是通过研究，教育和干细胞工程的转化在心血管组织工程方面做出重大贡献。 在这种情况下，干细胞工程包括设计用于再生医学的细胞和药物递送结构，以及阐明细胞介导修复的基本科学原理。该提案的目的是创建一个无细胞的双生长因子递送系统，以招募内源性祖细胞并促进其长期存活，以及测试这种组合策略在促进新血管形成和改善心脏功能方面的功效。该提案的成功将使PI能够在心脏工程领域建立一个项目，特别关注设计细胞和药物输送系统。 心脏干细胞治疗在临床试验中表现出有限的疗效，但只有通过强大的细胞工程过程才能成为现实。 这种方法有可能通过利用人体自身的干细胞来改变干细胞治疗。 此外，PI的工程方法将被用作一个平台，围绕这个平台，一系列的教育和推广目标将被met.Intellectual Merit：在工程支架合成和加工的新技术的进展可能允许进入心脏治疗的新阶段。 天然和合成基质已显示出作为递送生长因子和细胞的工具的前景;然而，迄今为止，这些构建体都没有表现出必要的时间和空间控制。递送多种生长因子以在精确组织的呈现中提供驻留干细胞的动员和存活的组合为心脏治疗的挑战提供了现实的解决方案。 PI将研究该系统是否能够以控释动力学递送多种生长因子。将评估联合策略（协同干细胞募集和持续细胞活力）的疗效，并探索潜在机制。 更广泛的影响：心脏再生的承诺只能通过分子和细胞水平上设计的解决方案来实现。 本项目的目标是提供两个功能：（1）设计一个独特的递送平台，可以控制干细胞组织和（2）阐明细胞介导的心脏修复的基本机制。 教育和推广目标通过工程设计的意识形态概念紧密联系在一起。 作为一名初级教师，PI已经构思并实施了UT奥斯汀的整个BME高级设计序列。 她对设计及其教学有着强烈而持续的热情，并建议设计应融入所有教育层次。 本提案中所述的外联活动从大学预科一直延伸到本科生。 将开发具体的工具，包括教学模块，在线课程资源，以及现有的大学预科推广计划使用的教学工具。